AIM:To investigate the effects of ethane 1,2-dimethanesulfonate (EDS) preconditioning on renal ischemia/reperfusion (I/R) injury in male Sprague-Dawley (SD) rats.METHODS: Male SD rats (n=48) were ran-domly assigned to 6 groups:blank, sham, I/R, EDS+I/R, EDS+testosterone (TST) +I/R, and castration (Cast)+I/R.The renal pedicles were bilaterally occluded with a microvascular clamp for 45 min to establish renal I/R-induced in-jury model.Bilateral orchiectomy was conducted 2 weeks before surgery .EDS (75 mg/kg) was intraperitoneally injected 5 d before operation .Blood samples were collected 24 h after reperfusion from the vena orbitalis posterior plexus .Luteinizing hormone (LH), TST, serum creatinine (SCr), blood urea nitrogen (BUN), and kidney injury molecule-1 (KIM-1) were detected.The renal tissues were harvested to measure the level of TNF-αand the expression of Fas mRNA and caspase-3 protein.RESULTS:Serum TST levels in EDS +I/R group and Cast +I/R group were below the minimum detectable threshold.Compared with other groups , the rats in EDS+I/R group and Cast +I/R group had higher levels of SCr , BUN and KIM-1 (P<0.05).SCr and BUN levels showed no significant difference between EDS +I/R group and Cast +I/R group (P>0.05), but KIM-1 level in EDS+I/R group was lower than that in Cast +I/R group (P<0.05).After reper-fusion for 24 h, the levels of TST and LH in EDS +I/R group, Cast+I/R group and EDS+TST+I/R group were lower than those 1 h before operation (P<0.05).Compared with Cast+I/R and I/R group, the TNF-αlevel and expression of Fas mRNA and caspase-3 protein were significantly decreased in EDS +I/R group ( P<0.05 ) .CONCLUSION: EDS preconditioning substantially reduces the serum TST level , thus attenuating I/R-induced acute renal injury .TNF-α-induced Fas/FasL pathway may be involved in this process .